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Regulation of the interferon lamda receptor by influenza

Award Number: R01HL081784
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Regulation of the interferon lamda receptor by influenza - Influenza is a leading cause of death in the US with a staggering economic burden. Interferons serve as a critical response to this virus triggering elaboration of host defense molecules within alveolar macrophages. A relatively new and unchartered area in interferon biology involves interferon lamda (IFN) acting through its cognate receptor, IFNLR1, to mediate anti-viral defense. Loss of IFNLR1 leads to viral dissemination and death in experimental influenza. The mechanistic platform of this proposal resides on our discovery of a unique molecular model whereby a protein, Fbxo45, rapidly impairs host defense by mediating ubiquitin-driven disposal of this crucial cytoprotective, anti-viral receptor, IFNLR1. Hence, in this application we will first elucidate how short-term influenza infection depletes IFNLR1 through Fbxo45, thereby accentuating experimental viral lung injury (Aim 1). We will specifically elucidate how Fbxo45 targets IFNLR1 for its degradation using complementary in vitro and in vivo genetic models. Next, after sustained influenza infection we observed that IFNLR1 mRNA levels increase in macrophages, perhaps as a compensatory host defense mechanism. Here we will assess novel post-transcriptional mechanisms mediated by microRNA acting on the 3’UTR of the IFNLR1 gene (Aim 2). These studies will provide a new pathobiologic model of lung injury that will serve as a platform for unveiling new molecular insight into the IFN- IFNLR1 axis that is indispensable to resolve inflammatory injury in subjects with severe virally-driven critical illness.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $545,431 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	000	15	6/28/2024	NON-COMPETING CONTINUATION	$545,431
														Subtotal = $545,431

Issue Date FY: 2023 ( Subtotal = $556,562 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	000	14	5/23/2023	NON-COMPETING CONTINUATION	$556,562
														Subtotal = $556,562

Issue Date FY: 2022 ( Subtotal = $556,271 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	001	13	8/27/2022	NON-COMPETING CONTINUATION	$556,562
2022	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	000	11	6/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$291
														Subtotal = $556,271

Issue Date FY: 2021 ( Subtotal = $556,562 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	000	12	7/26/2021	COMPETING CONTINUATION	$556,562
														Subtotal = $556,562

Issue Date FY: 2020 ( Subtotal = -$1 )
2020	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	000	11	9/29/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1
														Subtotal = -$1

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	001	11	3/18/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2019	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	003	11	3/22/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$69,367
2019	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	10	3/15/2019	NON-COMPETING CONTINUATION	-$1
2019	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	002	10	3/22/2019	NON-COMPETING CONTINUATION	-$69,367
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $385,000 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	10	3/16/2017	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2016 ( Subtotal = $385,000 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	9	2/24/2016	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2015 ( Subtotal = $379,225 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	8	3/3/2015	NON-COMPETING CONTINUATION	$379,225
														Subtotal = $379,225

Issue Date FY: 2014 ( Subtotal = $385,000 )
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	7	7/18/2014	COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2012 ( Subtotal = $0 )
2012	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	6	2/29/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $330,990 )
2010	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	002	6	3/8/2010	NON-COMPETING CONTINUATION	$330,990
2010	2009	UNIVERSITY OF IOWA	2 GILMORE HALL	IOWA CITY	IA	52242	JOHNSON	USA	Trans-NIH Recovery Act Research Support	004	4	8/24/2010	SUPPLEMENT FOR EXPANSION	-$8,000
2010	2009	UNIVERSITY OF IOWA	2 GILMORE HALL	IOWA CITY	IA	52242	JOHNSON	USA	Lung Diseases Research	001	4	12/11/2009	NON-COMPETING CONTINUATION	-$158,000
2010	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Recovery Act Research Support	003	5	8/24/2010	SUPPLEMENT FOR EXPANSION	$8,000
2010	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	5	12/11/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$158,000
														Subtotal = $330,990

Issue Date FY: 2009 ( Subtotal = $338,583 )
2009	2009	UNIVERSITY OF IOWA	2 GILMORE HALL	IOWA CITY	IA	52242	JOHNSON	USA	Lung Diseases Research	000	4	3/18/2009	NON-COMPETING CONTINUATION	$322,251
2009	2009	UNIVERSITY OF IOWA	2 GILMORE HALL	IOWA CITY	IA	52242	JOHNSON	USA	Trans-NIH Recovery Act Research Support	001	4	6/5/2009	SUPPLEMENT FOR EXPANSION	$16,332
														Subtotal = $338,583

Issue Date FY: 2008 ( Subtotal = $322,251 )
2008	2008	UNIVERSITY OF IOWA	2 GILMORE HALL	IOWA CITY	IA	52242	JOHNSON	USA	Lung Diseases Research	000	3	2/18/2008	NON-COMPETING CONTINUATION	$322,251
														Subtotal = $322,251

Issue Date FY: 2007 ( Subtotal = $322,251 )
2007	2007	UNIVERSITY OF IOWA	2 GILMORE HALL	IOWA CITY	IA	52242	JOHNSON	USA	Lung Diseases Research	000	2	3/15/2007	NON-COMPETING CONTINUATION	$322,251
														Subtotal = $322,251

Issue Date FY: 2006 ( Subtotal = $331,875 )
2006	2006	UNIVERSITY OF IOWA	ROOM B5K, JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Lung Diseases Research	000	1	2/28/2006	NEW	$331,875
														Subtotal = $331,875

Grand Total All Awards = $5,395,000

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Regulation of the interferon lamda receptor by influenza

Award Number: R01HL081784

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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